title: Antiviral hyperactivation-limiting therapeutics as a novel class for the treatment of HIV/AIDS: focus on VS411.
abstract: BACKGROUND
  Immune activation plays a central pathogenetic role in both HIV-1 replication and depletion of CD4(+) T cells leading to disease progression and the onset of the AIDS. While current antiretroviral therapies suppress viral replication to undetectable levels, they do not normalize the excessive level of T-cell activation and proliferation. A new class of anti-HIV-1 drugs known as antiviral hyperactivation-limiting therapeutics (AV-HALTs) combines direct antiviral activity with an antiproliferative action to limit the hyperactivation of the immune system now recognized as the key driver of the progressive loss of CD4(+) T cells that occurs over the natural course of the HIV-1 infection.
  
  
  METHODS
  Areas covered include preclinical, Phase I and Phase IIa studies of VS411, the first drug product in a novel class of anti-HIV drugs, AV-HALT agents.
  
  
  CONCLUSIONS
  The two drug combination VS411 safely achieved the goals established for the AV-HALT class based on the results of a Phase IIA proof-of-concept study. Additional work is underway to identify and develop new agents that combine the dual attributes of AV-HALTs, direct reduction of both HIV-1 viral load and markers of excessive immune activation, in a single molecule.
authors.affiliation: Fondazione "IRCCS Policlinico San Matteo", Infectious Disease Department, Piazzale Golgi 19, Pavia, Italy. a.uglietti@smatteo.pv.it
authors.forename: Alessia
authors.initials: A
authors.lastname: Uglietti
authors.forename: Renato
authors.initials: R
authors.lastname: Maserati
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002986:Clinical Trials as Topic; D016049:Didanosine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008213:Lymphocyte Activation; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D004338:Drug Combinations; C559378:VS411 drug combination; D014508:Urea; D016049:Didanosine; D006918:Hydroxyurea